PROJECT SUMMARY/ABSTRACT The normal platelet count in human blood is 150,000-400,000/?L, and these platelets are responsible for efficient hemostatic surveillance and bleeding mitigation in the body. Thrombocytopenia (TCP, low platelet count) is a condition caused by a decrease in platelet production, increase in platelet destruction or consumption, or increase in splenic sequestration. The age-adjusted prevalence of immune thrombocytopenic purpura (ITP) is estimated to be 9.5 per 100,000 persons in the USA, while drug-induced TCP affects 1-2 per 100,000 persons. The majority (>95%) of TCP cases result from autoimmune disorders or are induced by chemo- and radiotherapies as well as other pharmaceuticals. At platelet counts <50,000/?L, surgical procedures are complicated by high bleeding risks and any minor injury may lead to excessive bleeding. At counts <10,000/?L, spontaneous bleeding becomes a major concern. Therefore, frequent therapeutic and prophylactic platelet transfusions are required to increase platelet counts and mitigate bleeding risks. However, the availability of natural platelet products is severely limited by a near-static pool of donors and a very short shelf-life (3-5 days) due to high risks of bacterial contamination and storage-related platelet activation and degranulation. Therefore, there exists a significant unmet clinical need for a therapeutic agent that can mitigate bleeding complications intravenously in TCP patients, while allowing reduced contamination and long shelf-life without compromising function. To this end, we have developed a synthetic hemostatic nanotechnology, called SynthoPlateTM, that mimics platelet?s ability to adhere and aggregate specifically at a site of injury in the body. This technology has demonstrated platelet-mimetic hemostatic functions in vitro as well as in vivo in proof-of-concept murine and porcine models of bleeding. Building on this preliminary data, this proposal aims to establish the minimum and maximum effective doses of SynthoPlateTM needed to enhance clotting properties in vitro and mitigate bleeding in vivo in a mouse model of TCP. Success with the aims of this Phase I SBIR proposal will establish SynthoPlateTM as an innovative intravenously transfusable technology to mitigate bleeding complications in TCP. Furthermore, successful therapeutic demonstration with SynthoPlateTM in TCP mice will allow subsequent dosing, safety, toxicity and efficacy studies with GMP-manufactured SynthoPlate in large animal models, thus allowing IND-enabling studies towards clinical development, envisioned in Phase II.